A patient with AKI after cardiac surgery.
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ABSTRACT:
SUBMITTER: Tolwani AJ
PROVIDER: S-EPMC4123401 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
Publications
A patient with AKI after cardiac surgery.
Clinical journal of the American Society of Nephrology : CJASN 20140320 8
Up to 30% of patients undergoing cardiac surgery develop AKI, with 1% requiring RRT. AKI is an independent risk factor for morbidity and mortality. Postoperatively, even minimal changes in serum creatinine are associated with a substantial increase in mortality. No intervention has been definitely proven effective in reducing kidney injury. The successful prevention and management of AKI involves identifying patients at risk for AKI, recognizing subtle abnormalities in a timely manner, performin ...[more]
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Project description:Approximately 18% of patients undergoing cardiac surgery experience AKI (on the basis of modern standardized definitions of AKI), and approximately 2%-6% will require hemodialysis. The development of AKI after cardiac surgery portends poor short- and long-term prognoses, with those developing RIFLE failure or AKI Network stage III having an almost 2-fold increase in the risk of death. AKI is caused by a variety of factors, including nephrotoxins, hypoxia, mechanical trauma, inflammation, cardiopulmonary bypass, and hemodynamic instability, and it may be affected by the clinician's choice of fluids and vasoactive agents as well as the transfusion strategy used. The risk of AKI may be ameliorated by avoidance of nephrotoxins, achievement of adequate glucose control preoperatively, and use of goal-directed therapy hemodynamic strategies. Remote ischemic preconditioning is an exciting future strategy, but more work is needed before widespread implementation. Unfortunately, there are no pharmacologic agents known to reduce the risk of AKI or treat established AKI.
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Project description:AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%-79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%-20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.
| S-EPMC5791058 | biostudies-literature
Project description:Background As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass.Methods On the first day of serum creatinine-defined AKI, we measured urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days).Results In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively.Conclusions If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.
| S-EPMC5967766 | biostudies-literature
Project description:Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.
| S-EPMC3380645 | biostudies-literature
Project description:Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.
| S-EPMC4657835 | biostudies-literature
Project description:Background and objectivesAKI is a serious complication after cardiac surgery. Although high urinary concentrations of the tubular protein uromodulin, a marker of tubular health, are associated with less AKI in animal models, its relationship in humans is unknown.Design, setting, participants, & measurementsA post hoc analysis of a prospective cohort study of 218 adults undergoing on-pump cardiac surgery between 2004 and 2011 was conducted. Multivariable logistic and linear regression analyses were used to evaluate the associations of preoperative urinary uromodulin-to-creatinine ratio with postoperative AKI (defined as a rise in serum creatinine of >0.3 mg/dl or >1.5 times baseline); severe AKI (doubling of creatinine or need for dialysis) and peak postoperative serum creatinine over the first 72 hours.ResultsMean age was 68 years, 27% were women, 95% were white, and the median uromodulin-to-creatinine ratio was 10.0 ?g/g. AKI developed in 64 (29%) patients. Lower urinary uromodulin-to-creatinine ratio was associated with higher odds for AKI (odds ratio, 1.49 per 1-SD lower uromodulin; 95% confidence interval, 1.04 to 2.13), which was marginally attenuated after multivariable adjustment (odds ratio, 1.43; 95% confidence interval, 0.99 to 2.07). The lowest uromodulin-to-creatinine ratio quartile was also associated with higher odds for AKI relative to the highest quartile (odds ratio, 2.94; 95% confidence interval, 1.19 to 7.26), which was slightly attenuated after multivariable adjustment (odds ratio, 2.43; 95% confidence interval, 0.91 to 6.48). A uromodulin-to-creatinine ratio below the median was associated with higher adjusted odds for severe AKI, although this did not reach statistical significance (odds ratio, 4.03; 95% confidence interval, 0.87 to 18.70). Each 1-SD lower uromodulin-to-creatinine ratio was associated with a higher adjusted mean peak serum creatinine (0.07 mg/dl per SD; 95% confidence interval, 0.02 to 0.13).ConclusionsLower uromodulin-to-creatinine ratio is associated with higher odds of AKI and higher peak serum creatinine after cardiac surgery. Additional studies are needed to confirm these preliminary results.
| S-EPMC5220649 | biostudies-literature
Project description:BACKGROUND:Acute kidney injury (AKI) is a common post-cardiac surgery complication and influences patient morbidity and prognosis. This study was designed to identify preoperative candidate urine biomarkers in patients undergoing cardiac surgery. METHODS:A prospective cohort study of adults undergoing cardiac surgery at increased risk for AKI at a single hospital between July 2010 and September 2012 was performed. The primary outcome was the development of AKI, defined as an absolute serum creatinine (SCr) level increase ≥ 0.5 mg/dL or a ≥ 50% relative increase within 72 h of surgery. A secondary outcome was development of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO). Urine collected by voiding within 4 h prior to surgery was used for proteomic analysis and confirmatory enzyme linked immunosorbent assays (ELISAs) studies. Biomarkers were tested for AKI-prediction using Cox and Snell R2, area under the receiver operating curve (AUROC), and percent of corrected classifications. To evaluate the added effect of each candidate biomarker on AKI discrimination, receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated. RESULTS:Forty-seven of 755 patients met screening criteria including 15 with AKI. Proteomic analysis identified 29 proteins with a significant ≥2-fold change. Confirmatory ELISA measurements of five candidate markers showed urinary complement factor B (CFB) and histidine rich glycoprotein (HRG) concentrations were significantly increased in patients with AKI. By multivariate analysis, NRI, and IDI the addition of CFB and HRG to the standard clinical assessment significantly improved risk prediction for the primary outcome. Only HRG was a significant predictor in the 21 patients with AKI defined by KDIGO criteria. CONCLUSIONS:Pre-operative urine measurement of CFB or HRG significantly enhanced the current post-surgery AKI risk stratification for more restrictive definition of AKI. HRG, but not CFB or clinical risk stratification, predicted AKI defined by KDIGO. The ability of these biomarkers to predict risk for dialysis-requiring AKI or death could not be reliably assessed in our study due to a small number of patients with either outcome.
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Project description:AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10-29 versus 6-21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.
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Project description:Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ?27 GT repeats), and defined AKI as an increase in serum creatinine ?0.3 mg/dl within 48 hours or ?50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.
| S-EPMC5084897 | biostudies-other
Project description:Importance:Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear. Objective:To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes. Design, Setting, and Participants:This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009. Children were followed up with telephone calls and an in-person visit at 5 years after their surgery. Exposures:Acute kidney injury defined as a postoperative serum creatinine rise from preoperative baseline by 50% or 0.3 mg/dL or more during hospitalization for cardiac surgery. Main Outcomes and Measures:Hypertension (blood pressure ?95th percentile for height, age, sex, or self-reported hypertension), microalbuminuria (urine albumin to creatinine ratio >30 mg/g), and chronic kidney disease (serum creatinine estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 or microalbuminuria). Results:Overall, 131 children (median [interquartile range] age, 7.7 [5.9-9.9] years) participated in the 5-year in-person follow-up visit; 68 children (52%) were male. Fifty-seven of 131 children (44%) had postoperative AKI. At follow-up, 22 children (17%) had hypertension (10 times higher than the published general pediatric population prevalence), while 9 (8%), 13 (13%), and 1 (1%) had microalbuminuria, an eGFR less than 90 mL/min/1.73 m2, and an eGFR less than 60 mL/min/1.73 m2, respectively. Twenty-one children (18%) had chronic kidney disease. Only 5 children (4%) had been seen by a nephrologist during follow-up. There was no significant difference in renal outcomes between children with and without postoperative AKI. Conclusions and Relevance:Chronic kidney disease and hypertension are common 5 years after pediatric cardiac surgery. Perioperative AKI is not associated with these complications. Longer follow-up is needed to ascertain resolution or worsening of chronic kidney disease and hypertension.
| S-EPMC5476457 | biostudies-literature